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Phase I Study of MK-0683 in Combination With Bortezomib in Participants With Multiple Myeloma (MK-0683-098)

Primary Purpose

Multiple Myeloma

Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Vorinostat
Bortezomib
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • is ≥20 years of age.
  • has an established diagnosis of MM based on the myeloma diagnostic criteria
  • has received at least 1 but not more than 3 prior anti-myeloma regimens and has progressive disease after the most recent treatment regimen
  • has adequate organ function

Exclusion Criteria:

  • has had a prior allogeneic bone marrow transplant or plans to undergo any type of bone marrow transplantation during the study
  • has known hypersensitivity to any components of vorinostat or bortezomib
  • has active hepatitis B or C, plasma cell leukemia, or is human immunodeficiency virus (HIV) positive
  • has had prior treatment with vorinostat or histone deacetylase (HDAC) inhibitors

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Vorinostat + Bortezomib

    Arm Description

    Participants undergo up to 3 successive 21-day treatment cycles. During Cycle 1, participants receive vorinostat (400 mg once daily [QD] on Days 1 through 14) + bortezomib (1.3 mg/m^2 intravenous [IV] on Days 1, 4, 8, and 11). If that dose is not well tolerated, during Cycle 2 participants receive vorinostat (400 mg QD on Days 1 through 14) + bortezomib (1.0 mg/m^2 IV on Days 1, 4, 8, and 11). If that dose is not well tolerated, during Cycle 3 participants receive vorinostat (300 mg QD on Days 1 through 14) + bortezomib (1.0 mg/m^2 IV on Days 1, 4, 8, and 11).

    Outcomes

    Primary Outcome Measures

    Number of Participants With Dose-Limiting Toxicity (DLT) During Cycle 1
    The number of participants with ≥1 DLT during Cycle 1 is reported. A DLT is defined as an event considered by the investigator to be related to study treatment, and either: 1) a Grade 3 or 4 non-hematologic event (except for manageable toxicity by supportive care or non-prohibited therapies, or a transient increase in alanine aminotransferase [ALT]/aspartate aminotransferase [AST]); or 2) a Grade 4 hematologic toxicity except neutropenia or hemoglobin decreased (neutropenia was a DLT if it was Grade 3-4 with fever ≥38.5°C; Grade 3-4 with an infection requiring antibiotic/antifungal therapy; or Grade 4 and lasting ≥5 days).

    Secondary Outcome Measures

    Full Information

    First Posted
    March 4, 2009
    Last Updated
    April 7, 2021
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00858234
    Brief Title
    Phase I Study of MK-0683 in Combination With Bortezomib in Participants With Multiple Myeloma (MK-0683-098)
    Official Title
    A Multicenter, Open-Label, Phase I Study of MK-0683 in Combination With Bortezomib in Patients With Relapsed and/or Refractory Multiple Myeloma
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    April 2021
    Overall Recruitment Status
    Completed
    Study Start Date
    February 13, 2009 (Actual)
    Primary Completion Date
    June 11, 2010 (Actual)
    Study Completion Date
    April 19, 2012 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Merck Sharp & Dohme LLC

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    The primary purpose of this clinical study is to determine the recommended clinical doses of vorinostat (MK-0683) and bortezomib administered in combination to participants with relapsed and/or refractory multiple myeloma (MM). It was hypothesized that administration of vorinostat in combination with bortezomib is sufficiently safe and tolerated well enough to permit further study in participants with relapsed and/or refractory MM. Study results are based on data collected up to the data cut-off date of 20-March-2011.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Multiple Myeloma

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Sequential Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    9 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Vorinostat + Bortezomib
    Arm Type
    Experimental
    Arm Description
    Participants undergo up to 3 successive 21-day treatment cycles. During Cycle 1, participants receive vorinostat (400 mg once daily [QD] on Days 1 through 14) + bortezomib (1.3 mg/m^2 intravenous [IV] on Days 1, 4, 8, and 11). If that dose is not well tolerated, during Cycle 2 participants receive vorinostat (400 mg QD on Days 1 through 14) + bortezomib (1.0 mg/m^2 IV on Days 1, 4, 8, and 11). If that dose is not well tolerated, during Cycle 3 participants receive vorinostat (300 mg QD on Days 1 through 14) + bortezomib (1.0 mg/m^2 IV on Days 1, 4, 8, and 11).
    Intervention Type
    Drug
    Intervention Name(s)
    Vorinostat
    Other Intervention Name(s)
    MK-0683, ZOLINZA™
    Intervention Description
    Vorinostat (MK-0683) three or four 100 mg capsules taken by mouth with food.
    Intervention Type
    Drug
    Intervention Name(s)
    Bortezomib
    Other Intervention Name(s)
    VELCADE®
    Intervention Description
    Bortezomib (1.0 or 1.3 mg/m^2) intravenous infusion.
    Primary Outcome Measure Information:
    Title
    Number of Participants With Dose-Limiting Toxicity (DLT) During Cycle 1
    Description
    The number of participants with ≥1 DLT during Cycle 1 is reported. A DLT is defined as an event considered by the investigator to be related to study treatment, and either: 1) a Grade 3 or 4 non-hematologic event (except for manageable toxicity by supportive care or non-prohibited therapies, or a transient increase in alanine aminotransferase [ALT]/aspartate aminotransferase [AST]); or 2) a Grade 4 hematologic toxicity except neutropenia or hemoglobin decreased (neutropenia was a DLT if it was Grade 3-4 with fever ≥38.5°C; Grade 3-4 with an infection requiring antibiotic/antifungal therapy; or Grade 4 and lasting ≥5 days).
    Time Frame
    Up to 21 days
    Other Pre-specified Outcome Measures:
    Title
    Number of Participants With an Adverse Event (AE)
    Description
    The number of participants with ≥1 AE is reported. An AE is any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study product(s), whether or not considered related to the use of the product(s).
    Time Frame
    Up to 346 days (up to 30 days after the final dose of study treatment)
    Title
    Area Under the Plasma Concentration-Time Curve From 0 to 24 Hours Postdose (AUC0-24hr) of Vorinostat Administered With Bortezomib on Days 1 and 11
    Description
    The AUC0-24hr of vorinostat in plasma on Days 1 and 11 is reported in participants who also received bortezomib.
    Time Frame
    Predose and 0.8, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose on Days 1 and 11

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    20 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: is ≥20 years of age. has an established diagnosis of MM based on the myeloma diagnostic criteria has received at least 1 but not more than 3 prior anti-myeloma regimens and has progressive disease after the most recent treatment regimen has adequate organ function Exclusion Criteria: has had a prior allogeneic bone marrow transplant or plans to undergo any type of bone marrow transplantation during the study has known hypersensitivity to any components of vorinostat or bortezomib has active hepatitis B or C, plasma cell leukemia, or is human immunodeficiency virus (HIV) positive has had prior treatment with vorinostat or histone deacetylase (HDAC) inhibitors
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Medical Monitor
    Organizational Affiliation
    Merck Sharp & Dohme LLC
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
    IPD Sharing URL
    http://engagezone.msd.com/ds_documentation.php
    Citations:
    PubMed Identifier
    26619834
    Citation
    Ogawa Y, Ogura M, Tobinai K, Ando K, Suzuki T, Watanabe T, Ohmachi K, Uchida T, Hanson ME, Tanaka Y, Koh Y, Shimamoto T, Hotta T. A phase I study of vorinostat combined with bortezomib in Japanese patients with relapsed or refractory multiple myeloma. Int J Hematol. 2016 Jan;103(1):25-33. doi: 10.1007/s12185-015-1897-7. Epub 2015 Nov 30.
    Results Reference
    result

    Learn more about this trial

    Phase I Study of MK-0683 in Combination With Bortezomib in Participants With Multiple Myeloma (MK-0683-098)

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